Covalent HLA-B27/peptide complex induced by specific recognition of an aziridine mimic of arginine
- Author(s): Weiss, GA
- Valentekovich, RJ
- Collins, EJ
- Garboczi, DN
- Lane, WS
- Schreiber, SL
- Wiley, DC
- et al.
Published Web Locationhttps://doi.org/10.1073/pnas.93.20.10945
The class I major histocompatibility complex (MHC) glycoprotein HLA-B27 binds short peptides containing arginine at peptide position 2 (P2). The HLA- B27/peptide complex is recognized by T cells both as part of the development of the repertoire oft cells in the cellular immune system and during activation of cytotoxic T cells. Based on the three-dimensional structure of HLA-B27, we have synthesized a ligand with an aziridine-containing side chain designed to mimic arginine and to bind covalently in the arginine-specific P2 pocket of HLA-B27. Using tryptic digestion followed by mass spectrometry and amino acid sequencing, the aziridine-containing ligand is shown to alkylate specifically cysteine 67 of HLA-B27. Neither free cysteine in solution nor an exposed cysteine on a class 11 MHC molecule can be alkylated, showing that specific recognition between the anchor side-chain pocket of an MHC class I protein and the designed ligand (propinquity) is necessary to induce the selective covalent reaction with the MHC class I molecule.
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